Emerging Targets in Non-Small Cell Lung Cancer.

Lung cancer is responsible for a high burden of disease globally. Over the last two decades, the discovery of targetable oncogenic genomic alterations has revolutionized the treatment landscape for early-stage and advanced non-small cell lung cancer (NSCLC). New molecular drivers continue to emerge as promising therapeutic targets, including KRAS non-G12C, RAF/MEK, HER3, Nectin-4, folate receptor alpha, ITGB6, and PRMT5. In this review, we summarize the emerging molecular targets with a potential clinical impact in advanced NSCLC, elaborating on their clinical characteristics and specific mechanisms and molecular pathways for which targeted treatments are currently available. Additionally, we present an aggregate of ongoing clinical trials investigating the available treatment options targeting such alterations, in addition to their current recruitment status and preliminary efficacy data. These advancements may guide further research endeavors and inform future treatment strategies to improve the management of and transform outcomes for patients with advanced NSCLC.

Immunotherapy-Based Neoadjuvant Treatment of Advanced Microsatellite Instability-High Gastric Cancer: A Case Series.

Despite the use of first-line therapies like fluoropyrimidine and platinum-based cytotoxic chemotherapy, gastric cancer (GC) continues to carry a poor prognosis. Recent subgroup analyses of first-line phase III trials have demonstrated that patients with microsatellite instability-high (MSI-H) metastatic GC derive significant improvement in survival rates when immune checkpoint inhibitors (ICIs) are combined with chemotherapy compared with chemotherapy alone. However, it remains to be seen whether the success of ICIs in the metastatic setting can be translated into earlier stages of GC with resectable disease. We report 6 cases of locally advanced, nonmetastatic MSI-H GC that all demonstrated favorable response following treatment with pembrolizumab in addition to neoadjuvant chemotherapy. With the exception of immune-related colitis in one patient, pembrolizumab was well-tolerated. To our knowledge, this is the first reported US case series of patients treated with an ICI in combination with neoadjuvant chemotherapy for advanced, nonmetastatic, resectable or unresectable MSI-H GC.

Comparison of critically ill patients from three freestanding ED's compared to a tertiary care hospital based ED.

BACKGROUND: Freestanding emergency departments (FEDs) care for all patients, including critically ill, 24/7/365. We characterized patients from three FEDs transferred to intensive care units (ICU) at a tertiary care hospital, and compared hospital length of stay(LOS) between patients admitted to ICUs from FEDs versus a hospital-based ED (HBED). METHODS: We performed a retrospective, observational cohort study from January 2014 to December 2016. Demographic and clinical information was compared between FED and HBED patients with chi-square and fisher's exact tests for categorical variables and Student's t-test for continuous variables. The main outcome of interest was hospital LOS. Multi-variable linear regression was performed to estimate association between LOS and emergency facility type, while adjusting for potential confounders. RESULTS: We included 500 critically ill patients (FED = 250 and HBED = 250). Patients did not differ by age, gender, or BMI. FED patients were more likely to be white (89.6% vs. 70.8%, p < 0.001) and have higher Charlson Co-morbidity Index scores (3.5 vs. 2.4, p < 0.001). Average LOS for FED patients was 5 days, compared to 7 days for HBED patients (p < 0.001). After adjusting for demographic and clinical confounders, there was significant correlation between ED facility type and LOS in hospital (p < 0.001). CONCLUSION: Patients transferred from FEDs to an ICU were similar in age and gender, but more likely to be white with a higher Charlson Comorbidity Index score. FED patients experienced shorter hospital length of stay compared to patients admitted from a HBED.

Contrast-induced encephalopathy presenting as acute subarachnoid hemorrhage.

Contrast media induced encephalopathy is a rare complication of contrast administration characterized by non-specific neurological signs and symptoms that may present both clinically and radiolographically as subarachnoid hemorrhage. While there are few reported presentations in the neurology literature after inpatient contrast administration, similar emergency department presentations have not been documented. We describe a patient who presented with encephalopathy and expressive aphasia after outpatient evaluation of an intrathecal analgesia pump who had radiographic imaging consistent with acute subarachnoid hemorrhage. The hyperdensities seen on computed tomography scanning were subsequently identified as residual gadolinium contrast media resulting in allergic encephalopathy in this patient.

Methemoglobinemia: A Case Report.

Methemoglobinemia is a potentially life-threatening condition in which there is diminution of the oxygen-carrying capacity of circulating hemoglobin. It can result from either congenital or acquired processes. Methemoglobin forms when hemoglobin is oxidized to contain iron in the ferric (Fe3+) rather than the normal ferrous (Fe2+) state. Methemoglobinemia is a clinical diagnosis and is suspected in the presence of hypoxemia refractory to supplemental oxygen and the presence of chocolate-colored blood. Symptoms are usually dependent on methemoglobin levels; at levels higher than 35%, systemic symptoms from tissue hypoxia may be fatal. A high index of suspicion is required in patients with refractory hypoxia or cyanosis when treated with oxygen. Treatment options involve the removal of the inciting agent and treatment with the antidote methylene blue. Here we present a case of methemoglobinemia in a young patient who attended a college rave party.

Medullary carcinoma of the duodenum treated with pembrolizumab: a case report.

Background: Medullary carcinoma (MC) is a recognized histologic subtype of colorectal cancer characterized by poor glandular differentiation and intraepithelial lymphocytic infiltrate. However, MC originating from the small intestine is exceedingly rare, with only nine cases described in the literature. Based on previous cases, surgical resection is currently the mainstay of treatment for those with localized disease. We report the first case of a patient who presented with unresectable microsatellite instability-high (MSI-H) MC of the duodenum and was instead treated with pembrolizumab. Case Description: A 50-year-old man with history of adenocarcinoma of the proximal descending colon status post hemicolectomy and adjuvant treatment with chemotherapy and family history of Lynch syndrome presented with abdominal pain for two weeks. Computed tomography (CT) abdomen/pelvis revealed a 10.7 cm by 4.3 cm mass in the mid-portion of the duodenum abutting against the pancreatic head. Esophagogastroduodenoscopy (EGD) demonstrated circumferential, partially obstructing, intrinsic stenosis of the duodenum with ampullary involvement and likely invasion into the pancreatic head and common bile duct. Endoscopic biopsy of the primary tumor revealed poorly differentiated MC. Immunohistochemical staining showed loss of MLH1 and PMS2 expression. Staging with CT chest showed no evidence of disease. Positron emission tomography (PET) scan redemonstrated circumferential duodenal wall thickening and hypermetabolic activity with standardized uptake value (SUV) max of 26.4, as well as PET-avid epigastric, retroperitoneal, and periaortic lymphadenopathy suggestive of metastasis. He was started on pembrolizumab and found to have stable disease on repeat imaging along with significant improvement in symptoms and performance status. Conclusions: Due to the rarity of the tumor, there is no standardized approach to treatment. All patients in previously published cases underwent surgical resection. However, our patient was deemed a poor surgical candidate. Given his previous history of colon cancer and treatment with platinum-based therapy, he qualified for pembrolizumab as first line therapy for his MSI-H tumor. To our knowledge, this is the first report of MC of the duodenum as well as the first MC to be treated with pembrolizumab in the first line setting. In order to corroborate the use of immune checkpoint inhibitors as a treatment option for MC of the colon or small intestine, the aggregation of existing and future case data in this unique patient group is certainly warranted.

Leukemic infiltration of the optic nerve in chronic lymphocytic leukemia: A case report and review of literature.

Ophthalmic and neurologic involvement are rare complications of CLL, with few cases reported in the literature. We report a case of CLL with leukemic infiltration of the optic nerve and review of literature focusing on management and outcomes. A patient with heavily pretreated CLL presented to our hospital with progressive eye pain and was found to have infiltrative optic neuritis. CSF analysis confirmed involvement with CLL. After systemic treatment with R-CHOP and high-dose methotrexate, along with intrathecal cytarabine and hydrocortisone, she experienced significant improvement and was discharged home. Given the rarity of ophthalmic involvement in CLL, we reviewed all 15 previously reported cases of CLL with optic neuropathy as the first manifestation of CNS involvement and discussed the range of treatment options used and their respective outcomes.

A Focus on Intermediate-Risk Acute Myeloid Leukemia: Sub-Classification Updates and Therapeutic Challenges.

Acute myeloid leukemia (AML) represents a heterogeneous group of hematopoietic neoplasms deriving from the abnormal proliferation of myeloid progenitors in the bone marrow. Patients with AML may have highly variable outcomes, which are generally dictated by individual clinical and genomic characteristics. As such, the European LeukemiaNet 2017 and 2022 guidelines categorize newly diagnosed AML into favorable-, intermediate-, and adverse-risk groups, based on their molecular and cytogenetic profiles. Nevertheless, the intermediate-risk category remains poorly defined, as many patients fall into this group as a result of their exclusion from the other two. Moreover, further genomic data with potential prognostic and therapeutic influences continue to emerge, though they are yet to be integrated into the diagnostic and prognostic models of AML. This review highlights the latest therapeutic advances and challenges that warrant refining the prognostic classification of intermediate-risk AML.

Hemophagocytic Lymphohistiocytosis Complicated by Acute Respiratory Distress Syndrome and Multiorgan Failure.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition that is characterized by an overactive response of the immune system with excessive production of proinflammatory cytokines. Initial presentation of this condition often mimics and overlaps with many diseases including infections, sepsis, and multiorgan failure syndrome, which makes diagnosis the diagnosis of HLH challenging. Herein is described a case of a patient who developed acute respiratory distress syndrome and multiple organ failure related to HLH in a setting of probable viral pneumonia. The diagnosis was established based on laboratory and bone marrow biopsy findings. This patient was treated with the standard chemotherapy regimen of intravenous dexamethasone, etoposide in addition to intrathecal methotrexate for central nervous system involvement.

Synchronous Bilateral Primary Testicular Tumors With Discordant Histopathology.

Concomitant presentation of histologically distinct bilateral testicular tumors is exceedingly rare. Here we report the case of a 20-year-old male who presented with a left testicular mass. He was found to have bilateral testicular masses on ultrasound and underwent bilateral orchiectomy. Left testicular pathology revealed a mixed germ cell tumor consisting of teratoma, seminoma, and germ cell neoplasia in situ; right testicular pathology revealed two foci of pure seminomas. He is currently on active surveillance and remains in remission at 18-month follow-up. Our case demonstrates the rare occurrence of bilateral primary synchronous testicular tumors with different histopathology in each testis. Despite the rarity of this condition, its treatment is based on standard management of unilateral testicular carcinoma, with the added element of prioritization of one tumor over the other. It is important for clinicians to tailor management for bilateral testicular germ cell tumors according to the most aggressive component.

Transformation of Polycythemia Vera to Pure Erythroid Leukemia.

Pure erythroid leukemia (PEL) is an aggressive and exceedingly rare form of acute leukemia characterized as a neoplastic proliferation of immature cells committed to the erythroid lineage. It has a poor overall median survival of two to three months. To our knowledge, there are currently only a handful of reports of PEL arising from polycythemia vera. Most reported cases have been associated with radiation therapy or chemotherapeutic alkylating agents. Here we report a rare occurrence of polycythemia vera treated with phlebotomy and hydroxyurea that underwent leukemic transformation to pure erythroid leukemia.

Parotid adenocarcinoma metastasis to the breast: a case report.

Metastatic salivary gland tumors are rare clinical entities of the head and neck. Parotid gland carcinoma with distant metastases heralds a poor prognosis with a median survival of 4.3-7.3 months. The lungs, long bones, liver and brain are the most common sites of metastasis for parotid gland cancer, along with a few reported cases describing metastasis to the ileum, spleen and iliac crest. We present the first case to our knowledge of parotid adenocarcinoma metastasis to the breast.